Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
Harquail Centre for Neuromodulation, Sunnybrook Helth Sciences Centre, University of Toronto, Ontario, Canada.
Int J Pharm. 2024 Sep 5;662:124538. doi: 10.1016/j.ijpharm.2024.124538. Epub 2024 Jul 28.
Neuropathic pain is a high-intensity pain that can be caused by compression, transection, injury, nerve infiltration and drug treatment of cancer. Furthermore, drug therapy has low clinical efficacy, many adverse effects and remission of painful symptoms. In this way, natural products derived from plants constitute a promising therapeutic alternative. Therefore, the aim of this study was to evaluate the antihyperalgesic effect of γ-terpinene (γ-TPN) e γ-terpinene in β-cyclodextrin inclusion complexes (TPN/CD) on neuropathic pain induced by tumor cells. Complexation extended the effect time for another 5 h and daily treatment for six days with γ-TPN (50 mg/kg, p.o.) and γ-TPN/β-CD (50 mg/kg, p.o.) significantly reduced (p < 0.001) the mechanical hyperalgesia induced by the administration of 2x10 sarcoma cells 180 in the around the sciatic nerve. In addition, the Grip and Rota-rod techniques demonstrated that there was no interference on the muscle strength and motor coordination of the animals, suggesting that the compound under study does not have central nervous system depressant effects at the doses used. Molecular docking studies demonstrate favorable binding energies between γ-TPN and β-CD, and alpha-2 adrenergic, glutamatergic, opioid and cholinergic receptors. Thus, this study demonstrates the potential of terpinene complexation in controlling neuropathic pain induced by tumor cells.
神经病理性疼痛是一种高强度的疼痛，可由压迫、横断、损伤、神经浸润和癌症的药物治疗引起。此外，药物治疗的临床疗效低，不良反应多，疼痛症状缓解。在这种情况下，植物来源的天然产物构成了一种有前途的治疗替代物。因此，本研究旨在评估γ-萜品烯（γ-TPN）和β-环糊精包合物（TPN/CD）对肿瘤细胞诱导的神经病理性疼痛的抗痛觉过敏作用。包合作用将作用时间延长了另外 5 小时，每天用 γ-TPN（50mg/kg，po）和 γ-TPN/β-CD（50mg/kg，po）治疗六天，显著降低了（p<0.001）在坐骨神经周围给予 2x10 肉瘤细胞 180 后引起的机械性痛觉过敏。此外，握力和转棒技术表明，该化合物在使用的剂量下对动物的肌肉力量和运动协调没有干扰，这表明研究中的化合物没有中枢神经系统抑制作用。分子对接研究表明，γ-TPN 与 β-CD 以及α-2 肾上腺素能、谷氨酸能、阿片能和胆碱能受体之间具有有利的结合能。因此，本研究表明了萜烯复合物控制肿瘤细胞诱导的神经病理性疼痛的潜力。
